The present invention concerns a luminometer adapted for rapid assay of a large number of specimens of small volume, particularly in the field of medical assays.
The luminometer of the present invention is intend to be integrated into the movable head of an assay apparatus with multiple functions.
There are known luminometers permitting measurement of the light emitted during chemical reactions in specimens contained in plates, particularly so-called microtitration.
Thus there is described in U.S. Pat. No. 5,290,513 a luminometer comprising:
a base with a cover,
a first platform movable along the X axis, provided to receive a microtitration plate in the wells of which are distributed specimens of the product to be assayed.
a second platform movable along the Y axis, supporting a detector comprising a body, a head disposed at the end of an arm connected to said body, the body being articulated about an axis of an arm such as a record player arm with resilient return means adapted to press the head downwardly, in the Z direction.
This luminometer is also provided with a fixed mask for guidance and occlusion. This mask comprises a central groove oriented along the Y axis, so as to guide the head which is applied by resilient return means against the mask and more particularly in the groove, when the head is displaced along the Y axis.
A sealing sleeve completes the connection between the head and the groove to avoid penetration of parasitic photons.
The operation of this apparatus is as follows:
emplacement of a plate of specimens, the arm being raised and hence the head being retracted,
lowering of the arm and the head into the groove,
displacement of the plates stepwise along the X axis to assay all the specimens of one row, displacement of the head along the Y axis by one step to assay all the specimens of the following row, and so on.
Such a system permits applying the head with a given pressure against the mask, thereby ensuring good sealing, but this problem is actually transferred to the interface between the plate and the mask.
Also, this reference proposes pressing the microtitration plate against the lower surface of the mask by interposing a bit of foam between the microtitration plate and the platform which supports it, which rests at random over such a large surface without taking account of the fact that the return power of a foam is only difficultly controllable over all its surface.
It will be noted moreover that the detector is spaced from the measuring site by a distance equal to the length of the arm, which distance can only with difficulty be reduced because it is necessary to be able to have access to all of the surface of the microtitration plate, and also there is provided the interposition of a fiber optic connection.
The losses and errors arising from this connection are not negligible.
Such an apparatus solves some problems but gives rise to others. On the other hand, there results a certain compactness, which is very advantageous in assay laboratories and this advantage must be preserved and even improved for apparatus to come.
Another patent application, EP-A-181 060, discloses a measuring head permitting effecting sealing with the specimen support plate. In this embodiment, the detector is also distant from the measuring head and above all the specimen support plate is specific, according to a certain standardization.
Finally, it can be noted that there is not suggested, in this application, means for displacing the head along coordinates relative to the specimen support plate.
The object of the present invention is to overcome the drawbacks of the luminometers of the prior art by arranging a measuring detector directly on a support displaceable at least along Z such that it comes to bear directly on the reaction recesses as wells of a microtitration plate or on any other small volume container. This type of detector, developed and used in other applications particularly for transmission by optical fibers, is resistant to vibrations, to accelerations and to microshocks arising from high speed displacements. Its sensitivity is not necessarily as great as that of the detectors of the reaction photomultiplier type, but it is compensated in all cases by the proximity of the detector relative to the source of emission, by the fact that the connection is the transmission of an electric signal and not a luminous signal because the signal is transformed in the detector itself, and also by the fact that, as in the prior art, there are no disturbances engendered by photons that are external or simply emitted by the adjacent specimens, so called cross-contamination.
The invention also has for its object the integration of such luminometer in the working head of a particular apparatus ensuring also the measurement of several parameters having been the object of a patent application in the name of the present applicant and bearing the number EP-A-92/450 011. This apparatus, which is of very high performance, has a very high speed displacement head leading to accelerations of the order of 2 g.
To this end, the luminometer according to the invention comprises a chassis protected by a cover whose interior is accessible through a closure flap, a photon measuring detector with a measuring window, a support platform for specimen plates, fixed or with means to displace said plate along a system of orthogonal axes X, Y and Z, oriented preferably but not necessarily with the Z axis vertical, according to at least one of the axes of the plane X or Y, an electronic module for amplifying and digitizing data and an electronic module for processing these data, and this luminometer is characterized in that the measuring detector is movable and in that it comprises means for displacement in translation of this detector at least along the Z axis.
According to a preferred embodiment, the chassis is provided with displacement means in translation only, along one of the axes of the plane, the Y axis, and the detector and the means for displacement along the Z axis are carried by means for displacement in translation along the other of the axes of the planes, the X axis.
More particularly, the Z displacement means comprise a carriage mounted slidably on a rail oriented along the Z axis and a motor with an integrated encoder secured to a casing, driving a cam in rotation provided to ensure said translatory displacement, this casing being carried by a carriage mounted slidably on a rail, supported by a beam supported at one of its ends, oriented along the X axis, said carriage being driven by an assembly of a belt stretched between a roller and a pulley of a motor with an integrated encoder.
There is also provided an abutment at one of the ends of the movement in the X direction, provided with an end of path detector permitting initiating the displacements, with a black well permitting parking the detector sheltered from parasitic disturbances and with a calibrating lamp disposed in said black well permitting calibrating the detector as needed.
According to a particular embodiment, the electronic module for amplifying and digitizing the data is carried by the means for displacement along the X axis and is disposed in immediate adjacency to the detector.
The detector comprises a photomultiplier and an electronic module for the acquisition of integrated measurements, the assembly being protected by shielding.
According to an improvement of the invention, sealing means and means for compensating for planarity in line with the measuring window are added.
The invention also relates to a measuring device comprising at least one support for a microtitration plate, a movable head, provided with means for measuring the difference physico-chemical parameters, means for displacement in translation of said head along the X and Y axes, this device comprising a luminometer integrated in the head provided with the only means for displacement in translation along the Z axis.
The displacement cam of the preceding embodiment is replaced by a screw and nut assembly.